Selcuk Erdem

Increased preoperative levels of plasma fibrinogen and D dimer in patients with renal cell carcinoma is associated with poor survival and adverse tumor characteristics

BACKGROUND AND OBJECTIVE The relationship between renal cell carcinoma (RCC) and coagulation/fibrinolysis system has been described in several studies. The aim of this study was to investigate the role of 4 different coagulation/fibrinolysis factors on the prediction of histopathologic and survival prognosis in patients with RCC. PATIENTS AND METHODS Data from 128 patients who underwent surgical intervention between March 2006 and January 2011 for RCC were evaluated in this prospective study. Blood samples were collected from all patients on the morning of the operation to measure the plasma fibrinogen, D-dimer, coagulation factor VII, and antithrombin 3 levels. The relationships of these factors in the demographic, clinical, and histopathologic outcomes were analyzed using the Student t, Mann-Whitney U, Kruskal-Wallis, and one-way analysis of variance tests. Receiver operating curve analyses were performed to determine the optimal cutoff level for fibrinogen and d dimer, both of which had a strong relation with the clinical and histopathologic parameters. Disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using the Kaplan-Meier method. Multivariate Cox regression analyses (forward stepwise logistic regression) were performed to examine the independent prognostic values on survival outcomes. RESULTS Increased plasma fibrinogen and d-dimer levels were associated with tumor size (P = 0.004 and 0.106), nuclear grade (P<0.001 and<0.001), TNM category (P<0.001 and 0.029), and metastasis (P<0.001 and 0.032). Both increased plasma fibrinogen and d-dimer levels predicted decreased DFS (P = 0.027 and 0.04), CSS (P = 0.007 and 0.043), and OS (P = 0.014 and 0.001) rates based on Kaplan-Meier analyses. Furthermore, multivariate analyses demonstrated that fibrinogen independently predicted poor DFS (hazard ratio [HR] = 2.52; 95% CI: 1.04-6.31; P = 0.029) and CSS (HR = 3.89; 95% CI: 1.13-13.40; P = 0.032), whereas d dimer had negative independent prognostic value on OS (HR = 4.01; 95% CI: 1.54-10.50; P = 0.005). CONCLUSIONS Increased plasma fibrinogen levels accurately predict poor histopathologic and survival outcomes and may be an effective independent prognostic factor in patients with RCC. Moreover, d dimer may serve as a copredictive factor in conjunction with fibrinogen.

The Use of Self-Retaining Barbed Suture for Inner Layer Renorrhaphy Significantly Reduces Warm Ischemia Time in Laparoscopic Partial Nephrectomy: Outcomes of a Matched-Pair Analysis

PURPOSE To investigate the efficacy of self-retaining barbed suture (SRBS) on reducing renorrhaphy time and warm ischemia time (WIT) during laparoscopic partial nephrectomy (LPN), in comparison with conventional polyglactin suture. PATIENTS AND METHODS Between February 2008 and June 2012, 115 patients underwent LPN for renal tumors at our institution. Among them, the patients whose inner layer renorrhaphy was performed using SRBS (group 1, n=33) or polyglactin suture (group 2, n=33) were retrospectively identified from prospectively collected institutional laparoscopic database (unmatched comparison). Furthermore, 17 patients from each group were matched at a 1:1 ratio in terms of sex, age, body mass index, preoperative aspects and dimensions used for an anatomic (PADUA) classification scoring system, and operative approach (transperitoneoscopic/retroperitoneoscopic) to eliminate the effects of these variables on WIT (matched-pair comparison). Demographic, perioperative, and pathologic parameters were evaluated between groups in both unmatched and matched-pair comparison. RESULTS The perioperative parameters including inner layer renorrhaphy time, WIT, estimated blood loss, operative time, length of hospital stay, and complication rate were not statistically different between the two groups in the unmatched comparison. Median PADUA score (9 vs 8, P=0.006), median preoperative (4 cm vs 3.6 cm, P=0.049), and pathologic (4.5 cm vs 3.5 cm, P=0.009) tumor size, however, were significantly higher in group 1. In the matched-pair analysis, inner layer renorrhaphy time (350 sec vs 505 sec, P=0.004) and WIT (19 min vs 28 min, P=0.037) were significantly reduced with the use of SRBS in group 1 without a difference of median PADUA score (8 vs 8, P=1), median preoperative (3.8 cm vs 4 cm, P=0.959), and pathologic (4.2 cm vs 4 cm, P=0.284) tumor size. CONCLUSIONS The SRBS significantly reduced inner layer renorrhaphy time and WIT during LPN and may enable urologists to perform LPN in more challenging and larger tumors, in comparison with conventional polyglactin suture.

Up-regulation of TGM2 with ITGB1 and SDC4 is important in the development and metastasis of renal cell carcinoma

OBJECTIVE Tissue transglutaminase (TGM2) up-regulation is involved in the progression and dissemination of carcinomas through β1 integrin (ITGB1) association. Given that TGM2 interaction with syndecan-4 (SDC4) on the cell surface is important in the activation of ITGB1 and integrin-mediated survival signaling, we investigated the roles of TGM2, ITGB1, and SDC4 in the development and metastasis of renal cell carcinoma (RCC). MATERIAL AND METHODS Expression levels of TGM2, ITGB1, and SDC4 mRNA were analyzed in primary tumor samples (n = 95) and their healthy counterparts in addition to control and RCC epithelial cell lines. TGM2 catalytic activity in 60 randomly selected patient samples was measured by enzyme-linked sorbent plate assay. RESULTS TGM2 expression ratio showed a significant 2.9-fold decrease in 67 (70.5%) of the primary RCC tumors (P <0.0001) independent of clinical covariates, including tumor node metastasis (TNM) staging and histopathologic grading. For the remaining 28 (29.5%) tumors, a 1.95-fold increase was recorded in the TGM2 expression levels, which also showed a significant increase in ITGB1 and SDC4 expression levels in 82.6% of the overexpression cases (P <0.001). Up-regulation of TGM2 along with ITGB1 and SCD4 was associated with metastasis and a marked decrease in tumor necrosis. Consistently, RCC cell lines exhibited higher levels of TGM2 expression compared with the control epithelial cell line with a significant up-regulation of ITGB1 and SCD4 recorded for the metastatic lines. CONCLUSIONS Our findings suggest that TGM2 up-regulation along with ITGB1 and SDC4 plays an important role in the development of RCC tumors and advanced RCC with metastasis.

Urinary nerve growth factor in children with overactive bladder: A promising, noninvasive and objective biomarker

OBJECTIVE This prospective study was designed to determine urinary nerve growth factor (NGF) levels in children with overactive bladder (OAB), and to evaluate whether this factor can be used as a biomarker for diagnosis and monitoring treatment outcome. PATIENTS AND METHODS Urinary NGF levels were determined in 40 children with OAB and in a control group of 20 children with no urinary symptoms. Urine samples were collected from the patients prior to and at 3 and 6 months after the beginning of treatment. The total NGF levels (pg/mL) were further normalized to the concentration of urinary creatinine (NGF/Cr level). RESULTS Overall, both NGF and NGF/Cr levels were significantly higher at the beginning of the study. Mean NGF levels were 30.75 ± 8.35 and 9.75 ± 2.11 pg/ml (p = 0.023) and mean NGF/Cr levels were 0.53 ± 0.14 and 0.16 ± 0.04 (p = 0.022) in patients and controls, respectively. After 6 months of therapy, the NGF/Cr level was significantly reduced to almost control levels (0.16 ± 0.02, p = 0.047). CONCLUSION NGF and NGF/Cr levels were significantly higher in children with OAB than controls at initial evaluation. Furthermore, the NGF/Cr level was significantly reduced following 6 months of therapy. NGF and NGF/Cr levels show promise as reliable biomarkers for OAB diagnosis and to monitor therapy in the pediatric age group.

Nitric oxide synthase (eNOS4a/b) gene polymorphism is associated with tumor recurrence and progression in superficial bladder cancer cases.

PURPOSE We investigated the relationship between the distribution of the eNOS4a/b polymorphism and the clinical features of superficial bladder cancer. MATERIALS AND METHODS This study included 201 healthy controls with a mean ± SD age of 62.35 ± 7.96 years and 123 patients with a mean age of 64.03 ± 11.00 years diagnosed with histopathologically confirmed superficial bladder cancer. The eNOS4a/b polymorphism genotype (aa, bb or ab) was identified by polymerase chain reaction. Blood glutathione and plasma malondialdehyde levels were measured by spectrophotometry as an indicator of oxidative stress. We estimated total plasma levels of nitric oxide metabolites using a colorimetric assay kit. RESULTS There were no significant differences in age or body mass index between patients and controls. Malondialdehyde and nitric oxide metabolite levels were statistically significantly increased (p = 0.000 and 0.024, respectively) and glutathione levels were decreased (p = 0.000) in patients with superficial bladder cancer. The bb genotype of the eNOS4a/b polymorphism is the most frequent one in the Turkish population and the aa genotype was significantly more common in patients with superficial bladder cancer (p = 0.000). Also, the aa plus ab genotype was significantly more common in patients with high grade tumors (p = 0.013) and in those with more progression to muscle invasive disease (p = 0.000). This genotype was also a significant independent risk factor for recurrence after adjusting for smoking status, stage, grade and the presence of carcinoma in situ on logistic regression analyses (OR 3.095, 95% CI 1.21-7.86, p = 0.018). CONCLUSIONS The current study suggests that a genotype containing the a allele of the eNOS4a/b polymorphism may be a risk factor for bladder cancer. Additionally, patients harboring the aa plus ab genotype are more likely to experience tumor recurrence and progression.

Tunica Albuginea Decompression Fails to Alter the Injury of Prolonged Arterial Occlusion During Testicular Torsion

PURPOSE The correlation between intratesticular pressure during torsion/detorsion and subsequent testicular function and viability has been reported in several recent studies. We assessed the impact of tunica albuginea incision with tunica vaginalis flap coverage on intratesticular pressure and future histopathological parameters in a rat testicular torsion model. MATERIALS AND METHODS A total of 21 rats were divided into 3 groups. Group 1 consisted of 7 controls undergoing a sham operation, group 2 consisted of 7 animals undergoing torsion-detorsion, and group 3 consisted of 7 animals undergoing testicular torsion-detorsion followed by tunica albuginea incision and tunica vaginalis flap coverage. Torsion was created by 720-degree counterclockwise rotation of the left testis for 2 hours. By using a compartment monitor, the intratesticular pressure of the torsed testes was measured before torsion (pre-torsion), immediately before torsion repair (pre-detorsion), 5 minutes after detorsion (post-detorsion), and after tunical incision and tunica vaginalis flap application. The correlations between intratesticular pressure values and testicular weight, modified Johnsen score and mean seminiferous tubule diameter were evaluated 4 weeks postoperatively. RESULTS Median pre-detorsion intratesticular pressure was significantly decreased after detorsion in group 2 (21 vs 7 mm Hg, p <0.001) and group 3 (23 vs 7 mm Hg, p = 0.001). In addition, median intratesticular pressure after tunica albuginea incision and tunica vaginalis flap coverage in group 3 was significantly less compared to median post-detorsion intratesticular pressure in group 2 (5 vs 7 mm Hg, p = 0.025). Overall no significant difference was detected between groups 2 and 3 regarding median modified Johnsen score, mean seminiferous tubule diameter or median testicular weight. The significant reduction of intratesticular pressure in group 3 did not correlate with testicular weight (r = 0.500, p = 0.391), modified Johnsen score (r = -0.205, p = 0.741) or mean seminiferous tubule diameter (r = -0.200, p = 0.747). CONCLUSIONS Tunica albuginea decompression with tunica vaginalis flap coverage is an effective technique for decreasing intratesticular pressure in torsed testes. However, this technique failed to alter the injury of prolonged arterial occlusion in testicular torsion.

Laparoscopic Excision of Local Recurrence of Renal Cell Carcinoma

Laparoscopic excision of local recurrent renal cell carcinoma appears to be a feasible technique in wellselected patients with low-volume mass not involving adjacent organs.

Prospective evaluation of complications in laparoscopic urology at a mid-volume institution using standardized criteria: Experience of 1023 cases including learning curve in 9 years

Aim: To evaluate the laparoscopic operations performed in our department according to the modified Clavien classification system of complications. Materials and Methods: Between September, 2005 and February, 2014, a total of 1023 laparoscopic cases were performed. This period was divided into three terms (Terms 1, 2 and 3 consisting of 38, 32 and 32 months, respectively). According to the European Scoring System (ESS), easy (E), slightly difficult (SD), fairly difficult (FD), difficult (D), very difficult (VD) and extremely difficult (ED) cases were 35, 88, 170, 390, 203 and 137, respectively. The perioperative complications were evaluated based on the 3 time periods, with a specific emphasis on determining the learning curve according to the modified Clavien classification system of complications. Results: A total of 236 (23.1%) complications were observed according to the modified Clavien classification. The minor (Clavien I-II) and major (Clavien III, IV and V) complication rates were 20.5% (n = 210) and 2.4% (n = 26), respectively. Clavien I was the most frequently encountered type of complication (n = 120, %11.7). No significant difference was observed among all 3 time periods regarding total complication rates. The D cases had the highest complication rate compared to E, SD, FD, VD and ED cases among all three terms. The total number of complications increased significantly with increasing grade of technical difficulty according to the ESS. Conclusion: Complications encountered in our laparoscopic surgery experience were predominantly minor, and the rate of complications was not significantly increased during the learning curve. The present data can provide guidance and manage expectations for surgeons introducing laparoscopy into their practice.

Warm Ischemia-Related Postoperative Renal Dysfunction in Elective Laparoscopic Partial Nephrectomy Recovers During Intermediate-Term Follow-Up

PURPOSE To analyze the impact of warm ischemia time (WIT) on early postoperative and ultimate renal function after elective laparoscopic partial nephrectomy (LPN). PATIENTS AND METHODS One hundred and twenty-seven patients who underwent elective, ischemia-applied LPN were investigated in this study. The study patients were without stage 3 or greater chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m(2)) before LPN. Initially, the patients were grouped using the criteria of postoperative de novo stage 3 or greater CKD: Group A (n=104, eGFR ≥60 mL/min/1.73 m(2)) and group B (n=23, eGFR <60 mL/min/1.73 m(2)). The patients were also divided into two groups using 27.75 minute cutoff value obtained by receiver operating curve (ROC) analysis for WIT: Group 1 (n=69, WIT <27.75 min) and group 2 (n=58, WIT ≥27.75 min). The groups were compared with regard to demographic, perioperative, histopathologic, and renal functional outcomes. RESULTS The decreased preoperative eGFR (P<0.001) and increased WIT (P=0.007), operative time (P=0.015), diabetes mellitus (DM) rate (P=0.019) and pathologic tumor size (P=0.031) were significantly different in group B. Multivariate analysis determined that independent predictors of de novo stage 3 or greater CKD in the early postoperative period were preoperative eGFR (P<0.001), WIT (P=0.014), and DM (P=0.030); meanwhile, preoperative eGFR (P=0.006) was the only independent predictor at last follow-up. Decreased median postoperative eGFR (P=0.018) and percent preserved postoperative eGFR (P=0.001) were significantly different in the increased WIT group, as well as elevated median postoperative eGFR loss (P=0.001). After similar follow-up (26 vs 23.5 months, P=0.913), the increased and limited WIT groups were not significantly different with regard to final eGFR (P=0.936), final eGFR loss (P=0.749) and percent preserved final eGFR (P=0.690). CONCLUSIONS In elective LPN, increased WIT plays an important role in renal functional loss in the early postoperative period. This functional loss, however, recovered after an intermediate term follow-up period, similar to that of patients undergoing limited WIT.

Preoperative and Intraoperative Observations May Differ During Laparoscopic Nephron-Sparing Surgery

PURPOSE We retrospectively reviewed the preoperative radiologic findings and operational videos of a group of patients who were undergoing laparoscopic nephron-sparing surgery (NSS), to determine whether we should decide the operational approach (laparoscopic vs open or radical nephrectomy) on the basis of only the preoperative aspects and dimensions used for an anatomic (PADUA) classification. PATIENTS AND METHODS In total, 41 laparoscopic NSS operations were performed during a 34-month period for suspicious solid renal lesions. Clinicopathologic variables, PADUA scores, operative parameters, and renal functional outcomes were prospectively recorded and analyzed. Meanwhile, a similar classification (intraoperative aspects and dimensions used for an anatomic [IADUA] classification) was used to compare the preoperative imaging modality findings with intraoperative findings. RESULTS There was a 73.2% difference between PADUA and IADUA scores. Sixteen (39%) patients had PADUA scores >IADUA scores, 14 (34%) had PADUA scores <IADUA scores, and only 11 (27%) had similar PADUA and IADUA scores. For the study cohort, the mean operative time (OT) was 128 minutes (range 50-250) min, the mean estimated blood loss (EBL) was 199 mL (range 10-1000 mL), the mean warm ischemia time was 35.2 minutes (range 15-60 min), and the mean change in glomerular filtration rate was 8.17 mL/min/1.73m(2) (range -41-26 mL/min/1.73m(2)). The mean pathologic tumor size was 32.7±12.3 mm. Thirteen complications were recorded according to the modified Clavien system. PADUA and IADUA were not correlated with EBL and OT, and higher scores failed to predict perioperative complications. CONCLUSIONS Reproducible standardized classification systems are necessary for renal masses. Intraoperative findings for renal masses, however, may differ from the preoperative radiologic evaluation. Thus, the decision for the type of surgical approach should not be based solely on preoperative assessment, such as the PADUA score.